Biomedical subjects

Scott A Bradley

Publications and source records attributed to Scott A Bradley.

5 recordsLinked to original sources

PubMed2005

DOSY of sample-limited mixtures: comparison of cold, nano and conventional probes.

The DOSY analysis of dilute mixtures can be a challenge because a high signal-to-noise ratio is required for the best DOSY results. The sensitivity increase gained from new probe technologies (e.g. cold and nano probes) could enable one to acquire good DOSY spectra on sample amounts too low for conventional probes. In this article, we investigated the performance of cold and nano probes for qualitative DOSY analysis of concentrated and sample-limited mixtures, and compared the results with those of the conventional probe. We first measured the fluid flow for each probe. All three probes exhibited only relatively small levels of flow; consequently, a double-stimulated echo pulse sequence was not employed in the subsequent DOSY experiments. This decision was based on three facts: (1) flow-induced phase distortions were not observed, (2) our intentions are only to perform qualitative mixture analysis, and (3) discarding 50% of the already limited signal cannot be afforded. Although the cold and nano probes produced DOSY results for the concentrated mixture that were inferior to the conventional probe, the increase in the signal-to-noise ratio observed with these probes proved to be advantageous for the dilute three-component mixture. Furthermore, the cold probe showed slightly superior performance over the nano probe; thus, we conclude that among the probes examined the cold probe is best suited for qualitative DOSY analysis of sample-limited mixtures.

Amino Acids↗

PubMed2005

A modified CRISIS-HSQC for band-selective IMPRESS.

CRISIS (Compensation of Refocusing Inefficiency with Synchronized Inversion Sweep) is a powerful technique for obtaining multiplicity-edited HSQC spectra without compromising sensitivity. However, the stringent requirement for the duration of the CRISIS waveforms makes them unsuitable for other functions, such as band selection or IMPRESS (IMProved REsolution using Symmetrically Shifted pulses). We report here a modified CRISIS-gHSQC pulse sequence employing time-reversed 13C pi/2 EBURP-2 pulses. This IC-bs-gHSQC (IMPRESS-CRISIS-bs-gHSQC) sequence was found to be equally useful for acquiring multiplicity-edited, band-selective spectra individually or in tandem with IMPRESS. Remarkably, the latter provides multiple spectra in significantly less time and is the preferred approach when several crowded regions need to be assigned unambiguously. The use of adiabatic sweeps and the CRISIS pulses enable IC-bs-gHSQC to give better sensitivity than the original IMPRESS sequence for band-selective spectra.

Journal Article↗

PubMed2005

Simplifying DOSY spectra with selective TOCSY edited preparation.

Diffusion-ordered NMR spectroscopy, while quite powerful, is limited by its inability to resolve signals that are severely overlapped in the proton spectrum. We present here a DOSY experiment that uses selective TOCSY as an editing/preparation period. With this method, well-resolved signals of the analytes are selectively excited and the magnetization subsequently transferred by isotropic mixing to resonances buried in the matrix background, which are then resolved by the ensuing DOSY sequence. Key to the success of our proposed method is the incorporation of a highly effective zero-quantum filter into the selective TOCSY preparation period, which prevents zero-quantum coherence from being carried into the DOSY part of the pulse sequence. Further improvement in spectral resolution can be obtained by expanding the proposed experiment into a 3D sequence and utilizing the homonuclear decoupling feature of the BASHD-TOCSY technique. Both pulse sequences were found to greatly simplify the DOSY spectrum of a 'dirty' sucrose/raffinose mixture, as the complex matrix background is no longer present to obscure or overlap with the signals of interests. Furthermore, complete resolution of the relevant signals was achieved with the 3D sequence.

Carbohydrates↗

PubMed2005

A band-selective composite gradient: application to DQF-COSY.

We describe a unique band-selective method that utilizes a selective composite gradient to simultaneously achieve band selection and coherence pathway selection. This element is similar to the composite gradient known as the CLUB sandwich except the original broadband pulses have been replaced with selective pulses and the strengths of the antipolar gradients have been unbalanced. In this way, only the signals within the inversion band will continue to dephase throughout the duration of the element and satisfy the proper encoding-to-decoding gradient ratio necessary for coherence selection. Apart from the inverted polarity and asymmetry of the gradients, the band-selective CLUB sandwich is identical to the DPFGSE sequence and provides many of its desirable characteristics. We have successfully incorporated the band-selective CLUB into the DQF-COSY pulse sequence to create a band-selective experiment that offers the selectivity desired for resolution enhancement while maintaining excellent phase behavior. This is demonstrated on the congested aliphatic region of the ionophorous antibiotic Lasalocid A.

Algorithms↗

PubMed2004

Extending the limits of the selective 1D NOESY experiment with an improved selective TOCSY edited preparation function.

Compared to its 2D counterpart, the selective 1D NOESY experiment offers greatly simplified spectral interpretation and is invaluable to the structure elucidation of small-to-medium sized molecules, although its application is limited to well-resolved resonances only. The doubly selective 1D TOCSY-NOESY experiment allows the 1D NOESY experiment to be extended to resonances within overlapped spectral regions. However, existing methods do not address the critical issue of zero-quantum interference, which leads to severe anti-phase distortions to the line shape of scalar coupled spins and often complicates the identification of weak NOE enhancements. In this communication, we describe an improved selective TOCSY edited preparation (STEP) function and its application to the selective 1D NOESY experiment. The STEP function incorporates a novel zero-quantum filter introduced by Thrippleton and Keeler [Angew. Chem. Int. Ed. 42 (2003) 3938], which permits essentially complete suppression of zero-quantum coherence in a single scan. Residual anti-phase distortions due to spin-state mixing are removed using the double difference methodology reported by Shaka et al. [45th Experimental NMR Conference, Pacific Grove, USA, 2004]. The combined use of these techniques ensures that the final spectra are free of distortions, which is crucial to the reliable detection of weak NOE enhancements. Although employed as an additional preparation period in the example demonstrated here, the STEP function affords a general editing tool for spectral simplification and can be applied to a range of experiments.

Ionophores↗